INTRODUCTION
•Influenza is a serious respiratory illness of humans.
•Influenza pandemics have been associated with high
morbidity and mortality worldwide.
•Influenza A(H1N1) virus is a subtype of influenza A
virus and the most common cause of influenza(flu)
in humans.
•In 2009, the WHO declared the new strain of swine
origin H1N1 as a pandemic which is often referred as
“swine flu”.
What is Influenza (“flu”)?
•It is an acute
respiratory illness
caused by influenza
virus
•It infects the nose,
throat and lungs
•It is highly contagious
and spreads rapidly
from person to person
http://www.cdc.gov/flu/about/disease/
RNA
virus
Type A
ORTHOMYXOVIRIDAE
Family:
Genus:
Types
Specificity
Man
Animal
Birds
Man Man
Influenza virus
Type
B
Type
C
Influenza viruses
Single-stranded
http://emedicine.medscape.com/article/219557-
overview#a0101
80 to 120 nm
Lipidbilayer
16 types H1-H16
9 types N1-N9
Surface
antigens
Relevant parts of the virus
Subtypes of type A -depend on H & N antigens and are many.
Type B & C -not many subtype variations
H & N antigens of Influenza virus A change every year.
Neuraminidase(NA)
Haemaglutinin(HA)
http://emedicine.medscape.com/article/219557-overview#a0101
Pandemics of influenza
H1N1
H2N2
1889
Russian
influenza
H2N2
H2N2
1957
Asian
influenza
H2N2
H3N2
1968
Hong Kong
influenza
H3N2
H3N8
1900
Old Hong
Kong influenza
H3N8
1918
Spanish
influenza
H1N1
1915 1925 19551965 197519851995200518951905 2010 2015
2009
Pandemic
influenza
H1N1
H1N1
Pandemic
H1N1
The Novel 2009 H1N1 Virus
•Quadruple reassortmentvirus from pigs (North
American and Eurasian), Avian and human
2009 H1N1
virus
Replicates in the lungs more efficiently
How does it spread ?
Flu viruses spread mainly from
person to person through
coughing, sneezing, or talking to
someone with the flu.
Direct
contamination
The virus is transmitted by
respiratory aerosols (droplets)
loaded with virus that is expelled
during coughing & sneezing.
Respiratory
aerosols
(loaded with
virus)
Gets
infected
People with flu can spread it to
others up to about 6 feet away.
http://www.cdc.gov/flu/about/disease/spread.htm
How does it spread ?
People may also catch flu by touching their mouth
or nose after touching something with the virus on
it, such as doorknobs, tables, or an infected
person’s dirty hand.
Indirect
contamination
Infected
person
Gets
infected
http://www.cdc.gov/flu/about/disease/spread.htm
Source: Bean B, et al. JID 1982;146:47-51
Survival of Influenza Virus
Surfaces and Affect of Humidity & Temperature*
•Hard non-porous surfaces 24-48 hours
▫Plastic, stainless steel
Recoverable for > 24 hours
Transferable to hands up to 24 hours
•Cloth, paper & tissue
▫Recoverable for 8-12 hours
▫Transferable to hands 15 minutes
•Viable on hands <5 minutes only at high viral titers
▫Potential for indirect contact transmission
*Humidity 35-40%, Temperature 28
C (82 F)
How long can a person with the flu
spread the virus to other people?
Most people may be
able to spread the flu
from 1 day before
showing symptoms
to 5 to 7 days after
symptoms begin.
Some people, especially
young children and
peoplewith weakened
immune systems, might
be able to infect others
for an even longer time.
Somepersons can
be infected with
the flu virus but
have no symptoms.
During this time,
those persons may
still spread the
virus to others.
Symptoms start 1 to
4 days afterthe
virus enters the
body.
What are the signs and symptoms?
http://www.cdc.gov/flu/about/disease/symptoms.htm
>
38°C Any
2
SIGNS AND SYMPTOMS:
Lab tests not easily available & diagnosis is
clinical
If fever is accompanied with
any of these 2 signs and
symptoms, then diagnosis is
confirmed in 70% of cases
during the influenza season
Signs and symptoms
Two less common signs of the flu include:
Not everyone who
is sick with flu will
have all the signs
of the flu at the
same time.
It’s important to
note that not
everyone with flu
will have a fever.
These signs are more
common in children
than adults.
Case Definitions
A suspected case of Pandemic influenza A (H1N1)
virus infection is defined as a person with acute febrile
respiratory illness (fever ≥ 38 0 C) with onset.:
•within 7 days of close contact with a person who is a
confirmed case of pandemic influenza A (H1N1) virus
infection, or
•within 7 days of travel to community where there are one
or more confirmed pandemic influenza A(H1N1) cases,
or
•resides in a community where there are one or more
confirmed pandemic influenza cases.
Case Definitions
A probable case of Pandemic influenza A (H1N1)
virus infection is defined as a person with an acute
febrile respiratory illness who:
•is positive for influenza A, but unsubtypablefor H1 and
H3 by influenza RT-PCR or reagents used to detect
seasonal influenza virus infection, or
•is positive for influenza A by an influenza rapid test or an
influenza immunofluorescenceassay (IFA) plus meets
criteria for a suspected case
•individual with a clinically compatible illness who died of
an unexplained acute respiratory –illness who is
considered to be epidemiologically linked to a probable
or confirmed case.
Case Definitions
•A confirmed case of pandemic influenza A
(H1N1) virus infection is defined as a person with an
acute febrile respiratory illness with laboratory
confirmed pandemic influenza A (H1N1) virus
infection at WHO approved laboratories by one or
more of the following tests:
•Real Time PCR
•viral culture
•Four-fold rise in pandemic influenza A (H1N1) virus
specific neutralizing antibodies.
WHO IS AT RISK?????
EVERYONE IS AT RISK
•Children, Pregnant women, The elderly
(over 65)
•Those with chronic disease and underlying
health conditions
•Healthcare professionals
•Asthma
•Neurological and neurodevelopmental conditions
(cerebral palsy, epilepsy stroke, mental retardation,
moderate to severe developmental delay, muscular
dystrophy, or spinal cord injury)
•Chronic lung disease (chronic obstructive pulmonary
disease [COPD] and cystic fibrosis)
•Heart disease (congenital heart disease, congestive heart
failure and coronary artery disease)
•Blood disorders (sickle cell disease)
•Endocrine disorders (diabetes mellitus)
•Kidney disorders
•Liver disorders
•Metabolic disorders (inherited metabolic and
mitochondrial disorders)
•Weakened immune system due to disease or
medication (people with HIV or AIDS/cancer/those on
chronic steroids)
•People younger than 19 years of age who are
receiving long-term aspirin therapy
•People who are morbidly obese (Body Mass Index
(BMI) of 40 or greater)
“Emergency warning signs” in adults
“Emergency warning signs” in children
In infants
Also look for these warning signs: being unable to eat, having no tears
when crying, and having far fewer wet diapers than normal.
What are its complications?
Most people who get influenza will recover in a few days to less
than two weeks, but some people may develop complications like:
Some people are more likely to get flu complications that
result in being hospitalized& occasionallyresult in death.
The flu can make chronic health problemsworse.
Bacterial
pneumonia
For example, people with asthma may experience
asthma attacks while they have the flu, and people
with chronic congestive heart failure may have
worsening of this condition that is triggered by the
flu.
Bronchitis
Sinus/ear
infections
Dehydration
http://www.cdc.gov/flu/about/disease/symptoms.htm
DIAGNOSIS
Confirmation of Pandemic influenza A(H1N1)
infection is through:
•Real time RT PCR or
•Isolation of the virus in culture or
•Four-fold rise in virus specific neutralizing
antibodies.
•For confirmation of diagnosis, clinical specimens such as
nasopharyngeal swab, throat swab, nasal swab, wash or
aspirate, and tracheal aspirate (for intubatedpatients) are to
be obtained.
•The sample should be collected by a trained physician /
microbiologist preferably before administration of the anti-
viral drug.
•Keep specimens at 4°C in viral transport media until
transported for testing.
•The samples should be transported to designated laboratories
with in 24 hours.
•If they cannot be transported then it needs to b stored at -
70°C.
•Paired blood samples at an interval of 14 days for serological
testing should also be collected.
RT-PCR
•The Human Influenza Virus Real-Time RT-PCR is an
in vitro laboratory diagnostic test for direct molecular
identification of influenza isolates is a rapid and
powerful technique.
•Can provide results within 4 hours.
•It is the only in vitro diagnostic test for influenza that is
cleared by the FDA for use with lower respiratory tract.
•The RT-PCR allows template viral RNA to be reverse
transcribed producing complementary DNA(cDNA)
which can then be amplified and detected
.
The kit utilizes a 3-module design and can:
•Identify and distinguish between influenza A and B
viruses,
•Classify influenza A viruses by subtype, and
•Detect Pandemic influenza A (H1N1) 2009 strain
TREATMENT
The guiding principles are:
•Early implementation of infection control precautions
to minimize nosocomical/ household spread of
disease
•Prompt treatment to prevent severe illness & death.
•Early identification and follow up of persons at risk.
Guidelines on categorization of Seasonal
Influenza A H1N1 cases during screening for
home isolation, testing, treatment and
hospitalization (Revised on 11.02.2015)
•In order to prevent and contain outbreak of
Influenza-A H1N1 virus for screening, testing and
isolation following guidelines are to be followed:
•At first all individuals seeking consultations for flu
like symptoms should be screened at healthcare
facilities both Government and private or examined
by a doctor and these will be categorized as
Category-A
•Patients with mild fever plus cough / sore throat
with or without bodyache, headache, diarrhoeaand
vomiting will be categorized as Category-A.
•They do not require Oseltamivirand should be
treated for the symptoms mentioned above. The patients
should be monitored for their progress and reassessed at
24 to 48 hours by the doctor.
•No testing of the patient for H1N1 is required.
•Patients should confine themselves at home and avoid
mixing up with public and high risk members in the
family.
Category-B
(i) In addition to all the signs and symptoms mentioned under Category-A, if the
patient has high grade fever and severe sore throat, may require home
isolation and Oseltamivir;
(ii) In addition to all the signs and symptoms mentioned under Category-A,
individuals having one or more of the followinghigh risk conditions shall
be treated with Oseltamivir:
•Children with mild illness but with predisposing risk factors.
•Pregnant women;
•Persons aged 65 years or older;
•Patients with lung diseases, heart disease, liver disease kidney disease, blood
disorders, diabetes, neurological disorders, cancer and HIV/AIDS;
•Patients on long term cortisone therapy.
No tests for H1N1 is required for Category-B (i) and (ii).
All patients of Category-B (i) and (ii) should confine themselves at home and
avoid mixing with public and high risk members in the family.
Broad Spectrum antibiotics as per the Guideline for Community-acquired
pneumonia (CAP) may be prescribed.
Category-C
In addition to the above signs and symptoms of Category-A and
B, if the patient has one or more of the following:
•Breathlessness, chest pain, drowsiness, fall in blood pressure,
sputum mixed with blood, bluish discolourationof nails;
•Children with influenza like illness who had a severe disease
as manifested by the red flag signs (Somnolence, high and
persistent fever, inability to feed well, convulsions, shortness
of breath, difficulty in breathing, etc).
•Worsening of underlying chronic conditions.
All these patients mentioned above in Category-C require
testing, immediate hospitalization and treatment.
How does one manage influenza?
Treatment
1 Prevention
1
Drugs (antivirals)
•Antivirals
(chemoprophylaxis)
•Good health habits
•Vaccines
Adamantanes
•Amantadine
•Rimantadine
Neuraminidase Inhibitors (NAIs)
•Zanamivir
•Oseltamivir
•Peramivir
•Laninamivir
Vaccination is the most effective measure
at preventing influenza and its severe
outcomes.
2
2. http://www.apaci.asia/influenza/burden-of-influenza-a-benefit-of-vaccination
Everyone 6 months of age and older
should get a flu vaccine every season
(CDC)
3
3. http://www.cdc.gov/flu/protect/keyfacts.htm
1.http://www.who.int/mediacentre/factsheets/fs211/en/ last accessed on 19th January 2014
Mechanism of action of Antivirals
ADAMANTANES
NEURAMINIDASE
INHIBITORs
Adverse reactions:
•Oseltamiviris generally well tolerated
•Gastrointestinal side effects (transient nausea, vomiting)
may increase with increasing doses, particularly above 300
mg/day.
•Occasionally it may cause bronchitis, insomnia and
vertigo.
•Less commonly angina, pseudo membranous colitis and
peritonsillarabscess have also been reported.
•There have been rare reports of anaphylaxis and skin
rashes
Commencement within 12 h of symptom onset reduced
illness duration by 3.1 days (compared to 48 hrs treatment)
Early treatment with oseltamiviris
better!
Journal of Antimicrobial Chemotherapy 2003; 51: 123-129
Timely oseltamiviradministration has a beneficial
effect on outcomes in hospitalized adults
Chest 2011; 140(4):1025–1032
Time from onset of symptoms to oseltamiviradministration (+ 1-day
increase) was independently associated with a prolonged duration of the
fever, prolonged LOS, more-often need for mechanical ventilation, and
higher mortality
Oseltamivirreduces complications and antibiotic use in
influenza infected patients in healthy and high-risk patients
Risk for pneumonia approximately 50% lower than among those
persons receiving a placebo and 34% lower among patients at risk
for complications Arch IntMed 2003;163:1667-72
Benefits of oseltamivirin high-risk population with
chronic respiratory diseases
*
or cardiac disease
*chronic bronchitis, obstructive emphysema, bronchial asthma or
bronchiectasis
Oseltamivirgiven within 48 hours of symptom onset
significantly reduced:
•Duration of influenza symptoms by 36.8%
•Severity by 43.1%
•Duration of fever by 45.2%
•Time to return to baseline health status by 5 days
A decrease in the incidence of secondary complications
and antibiotic use, without increasing the total medical
cost noted.
Curr Med Res Opin. 2006 Jan;22(1):75-82.
Reduction in hospitalizations by 59% with
early oseltamivirtreatment
1. Arch IntMed 2003;163:1667-72
0.7% vs1.7%
1
2. The Lancet Infectious Diseases 2014; 14 (2): 109–118
1. http://www.cdc.gov/flu/news/flu-antiviral-benefits.htm
•Overall flu symptoms reduced by one day compared with placebo
(3 days versus 4 days)
•Reduced amount of live virus that was isolated from respiratory
specimens by 12% to 50% compared with placebo regardless of
whether treatment started before or after 2 days since illness
onset.
Oseltamivirtreatment within 5 days of symptom onset; Crowded, low-income, urban
community in Bangladesh, (mostly children< 5 years)
2
Treatment not to be delayed while awaiting diagnostic test results, nor
should it be withheld in patients with indications for therapy who present
>48 after the onset of symptoms
3
3. Int. J. Pharm. Sci. Rev. Res., 2014: 25(2), Article No. 48:
252-258
Dose of Zanamivir-Treatment
Adults and children > 5 years
•5 mg capsules to be inhaled
•2 inhalations twice a day with DPI
•2 doses on first day at least 2 hours apart
•Subsequently 12 hours apart
Warning
Generally not recommended for patients with asthma/COPD
Occasionally bronchospasmhas been reported. Keep
bronchodilator ready
Significant benefits with administration of
zanamivirwithin 48 hours
Rapid reduction of the viral load observed. The mean area under the
curve for viral load during the first 48 h of treatment was 8.48 log10 vRNAcopies/ml
x h lower in the zanamivirgroup compared with placebo
2
Meta-analysis of 7 trials showed:
1
•31% reduction of antibiotic prescription in zanamivir
•Lower incidence of complications (13% vs18%)
•Fewer nights of sleep disturbance (median 2 nights vs3 nights)
in asthma or COPD patients
•Reduced the incidence of complications (requiring antibiotics
and a change in respiratory medication) compared with placebo
by 58%
1.ClinDrug Invest 2000 Nov; 20 (5): 337-349
2.Scand J Infect Dis. 2003;35(1):52-8.
•Patients with signs of tachypnea, dyspnea, respiratory
distress and oxygen saturation less than 90 per cent
should be supplemented with oxygen therapy.
•Types of oxygen devices depend on the severity of
hypoxic conditions which can be started from oxygen
cannula, simple mask, partial re-breathing mask (mask
with reservoir bag) and non re-breathing mask. In
children, oxygen hood or head boxes can be used.
•Patients with severe pneumonia and acute respiratory
failure (SpO2 < 90% and PaO2 <60 mmHg with oxygen
therapy) must be supported with mechanical ventilation.
Invasive mechanical ventilation is preferred choice.
PREVENTION
If you get sick…
•Stay home if you’re
sick for 7 days
after your
symptoms
beginor until
you’ve been
symptom-free
for 24 hours,
whichever is
longer..
PERSONAL PROTECTION EQUIPMENTS
PPE reduces the risk of infection if used correctly. It
includes:
• Gloves (nonsterile),
• Mask (high-efficiency mask) / Three layered surgical
mask,
• Long-sleeved cuffed gown,
• Protective eyewear (goggles/visors/face shields),
• Cap (may be used in high risk situations where there may
be increased
aerosols),
• Plastic apron if splashing of blood, body fluids, excretions
and secretions is
anticipated.
How are vaccines helpful in
preventing flu?
•The best way to prevent the flu is by getting a flu
vaccine each year.
•Levels of protective antibodyagainst influenza
viruses can decline over the course of a year, so
even people who got a flu vaccine last year
should get vaccinated again this yearto ensure
that they are optimally protected.
•About two weeks after vaccination, antibodies
develop that protect against influenza virus
infection.
•Flu vaccines will not protect against flu-like
illnesses caused by non-influenza viruses.
When should one get vaccinated?
•To allow time for production of protective
antibody levels, vaccination should
optimally occur before onset of influenza
activity in the community.
•Vaccination also should continue to be
offered throughoutthe influenza season.
Seasonal Influenza A (H1N1): Guidelines for
Vaccination of Health Care Workers (Updated on
14th February 2015)
•World Health Organization recommends vaccination of high risk
groups with Seasonal Influenza Vaccination.
•Health Care Workers working in casualty/ emergency
department of identified hospitals treating Influenza cases.
•Heath Care Workers working in ICU and Isolation Wards
managing influenza patients.
•Health Care Workers identified to work in screening centres
that would be set up for categorization of patients during Seasonal
Influenza outbreak.
•Health Care workers treating/managing the High Risk Group
•Laboratory personnel working in virologicallaboratories testing
Influenza samples.
•Rapid Response Team members identified to investigate
outbreaks of Influenza.
•Drivers and staff of vehicles/ambulancesinvolved in transfer
of Influenza patients.
•The vaccine should be used every year.
•Influenza vaccination is most effective when circulating
viruses are well-matched with vaccine viruses.
•Even with appropriate matching, efficacy of vaccine may be
about 70% to 80%, especially in geriatric age group.
•In case the locally circulating virus is different from vaccine
virus recommended by WHO, it may not be effective at all.
•Hence, vaccine should not give a false sense of security.
Considering the risk perspective, the preventive modality of
infection prevention and control practices like use of PPEs
should be strictly adhered to.
•The available vaccine takes about 2-3 weeks for
development of immunity. The use of chemoprophylaxis
during this period may be considered.
MAJOR ISSUES
•Underutilization of vaccines
•Questionable efficacy of current vaccines
on 2014-2015 influenza virus
•Differences in perceptions/concepts for
influenza control
•Limited medical care and treatment delay